Usnic acid enantiomers restore cognitive deficits and neurochemical alterations induced by Aβ1–42 in mice
| Autor: | Márcia Maria de Souza, Tiago Coelho de Assis Lage, Ana Paula Dalmagro, Bernardo Carlesso Pinto, Camila André Cazarin, Thales Uchôa da Costa Sobrinho, Ângelo de Fátima, Luisa Mota da Silva, Ana Elisa Gonçalves, Luiz Carlos Klein-Júnior, Thaís Savoldi Lorenzett, Thaise Boeing, Rogério Corrêa, Sergio Antonio Fernandes |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Usnic acid Hippocampus Morris water navigation task Pharmacology Acetylcholinesterase 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine Neurochemical chemistry medicine Galantamine Donepezil 030217 neurology & neurosurgery Neuroinflammation 030304 developmental biology medicine.drug |
| Zdroj: | Behavioural Brain Research. 397:112945 |
| ISSN: | 0166-4328 |
| DOI: | 10.1016/j.bbr.2020.112945 |
| Popis: | Alzheimer's disease (AD) is the most prevalent form of dementia with a complex pathophysiology not fully elucidated but with limited pharmacological treatment. The Usnic acid (UA) is a lichen secondary metabolite found in two enantiomeric forms: (R)-(+)-UA or (S)-(-)-UA, with antioxidant and anti-inflammatory potential. Thus, given the role of neuroinflammation and oxidative injury in the AD, this study aimed to investigate experimentally the cognitive enhancing and anti-neuroinflammatory effects of UA enantiomers. First, the interactions of UA on acetylcholinesterase (AChE) was assessed by molecular docking and its inhibitory capability on AChE was assessed in vitro. In vivo trials investigated the effects of UA enantiomers in mice exposed to Aβ1−42 peptide (400 pmol/mice) intracerebroventricularly (i.c.v.). For this, mice were treated orally during 24 days with (R)-(+)-UA or (S)-(-)-UA at 25, 50, or 100 mg/kg, vehicle, or donepezil (2 mg/kg). Animals were submitted to the novel object recognized, Morris water maze, and inhibitory-avoidance task to assess the cognitive deficits. Additionally, UA antioxidant capacity and neuroinflammatory biomarkers were measured at the cortex and hippocampus from mice. Our results indicated that UA enantiomers evoked complex-receptor interaction with AChE like galantamine in silico. Also, UA enantiomers improved the learning and memory of the animals and in parallel decreased the myeloperoxidase activity and the lipid hydroperoxides (LOOH) on the cortex and hippocampus and reduced the IL-1β levels on the hippocampus. In summary, UA restored the cognitive deficits, as well as the signs of LOOH and neuroinflammation induced by Aβ1−42 administration in mice. |
| Databáze: | OpenAIRE |
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